The Integrated Female Sexually Transmitted Infection Testing for HIV Epidemic Control Through PrEP (IN-STEP) Study

NCT06743204 | Recruiting DMC

• 2 other identifiers: IRB00447136R01AI177132
• Study Type: interventional
• Target: 5,560
• Locations: 1 country
• Sites: 1

Brief Summary

Globally, new HIV infections are concentrated in eastern and southern Africa where the infections are largely acquired by women outside of known key populations. Identifying African women at high risk for HIV acquisition and successfully engaging them in HIV prevention services, particularly pre-exposure prophylaxis (PrEP) programs, is an urgent global health priority. The U.S. President's Emergency Plan for AIDS Relief program in Africa typically relies on self-reported risk screening tools (SRST) to target HIV testing and refer individuals for PrEP. However, these tools have low to moderate sensitivity, missing many women at high risk for HIV. This is partly due to underreporting of risk factors, but also because many African women are at heightened HIV risk solely through relationships with high-risk male partners. Moreover, many African women enrolled into PrEP programs stop using PrEP within months of initiation. Decades of research shows that curable sexually transmitted infections (cSTI) are objective markers of future HIV risk, but cSTI testing largely has been omitted from African HIV programs. With the advent of lower cost multiplex cSTI testing and point of care diagnostics, there is new opportunity to determine whether integrating female cSTI testing services into HIV programs can improve HIV epidemic control. Here, the investigators will conduct an individually randomized effectiveness implementation trial of SRST plus cSTI diagnostic testing for chlamydia, gonorrhea, trichomonas, and syphilis compared to SRST alone to increase PrEP use among cis-gender African women aged 15-39 years. The investigators hypothesize that cSTI testing will increase PrEP use primarily through (i) improved identification of women at high risk for HIV and (ii) enhancement of self-perceived HIV risk. The proposed research will be nested within the Rakai Community Cohort Study, a population-based HIV surveillance cohort in Uganda. In Aim 1, \~4,500 HIV-negative women will be individually randomized 1:1 to PrEP screening based on SRST plus cSTI diagnostic testing (intervention) versus PrEP screening based on SRST alone (control arm). Both arms will be offered syndromic case management for cSTIs and syphilis testing for pregnant women (standard of care). The primary outcomes will be PrEP uptake, adherence, and persistence, assessed through clinical records and drug level testing. In Aim 2, the investigators will perform a mixed-methods, implementation science evaluation of female cSTI testing for HIV prevention and control. The investigators will use qualitative and quantitative methods to assess the mechanisms, barriers, and facilitators to improving PrEP outcomes through cSTI testing and how this varies by cSTI pathogen, SRST outcomes, and demographic profiles. In Aim 3, the investigators will use mathematical models to evaluate different cSTI testing approaches to reduce HIV incidence at a population level by considering what cSTIs to screen for, in what health care settings, and at what cost thresholds. The investigators will also model broader health benefits of cSTI testing. Results from this study will provide actionable, population-level information to inform strategic delivery of high impact HIV prevention through integrated HIV and cSTI programming in Africa.

Conditions

Gonorrhea Female; Chlamydia Females; Syphilis Female; Trichomonas Vaginalis; HIV; PrEP Uptake

Keywords

Sexually Transmitted Infections (STI); Diagnostics; HIV; Women; Africa; Uganda; PrEP; Adolescent Girls and Young Women (AGYW)

Outcome Measures

Primary Outcomes (3)

• PreP uptake

  PrEP uptake will be defined as the proportion of HIV-negative women initially not taking PrEP at baseline who initiated PrEP by 3 months as determined from IN-STEP survey and clinical records.

  From enrollment up to 3 months post enrollment

• PreP adherence

  PrEP adherence will be defined as the proportion of HIV-negative women initially not taking PrEP with high-level adherence. Tenofovir diphosphate (TFV-DP) ≥800 fmol/punch at the 6-month IN-STEP visit.

  From enrollment up to 6 months post enrollment

• PreP persistence

  PrEP persistence will be defined as the proportion of HIV-negative women initially not taking PrEP with continuous attendance at quarterly PrEP program follow-up/refill visits through 6 months after PrEP initiation as validated through clinical records.

  From enrollment up to 6 months post enrollment

Study Arms (2)

IN-STEP Intervention

EXPERIMENTAL

Other: Self-Reported Risk Screening for PrEP and Diagnostic STI testing

Standard-of-Care

ACTIVE COMPARATOR

Other: Self-reported risk screening for PrEP and syndromic management for STIs

Interventions

Self-Reported Risk Screening for PrEP and Diagnostic STI testing OTHER

The intervention arm will include: 1) Standard-of-care STI symptom screening: The investigators will ask participants if any STI symptoms 2) PrEP screening (if HIV- only): PrEP eligibility screening will be done using the standard-care Ministry Health self-reported risk screening (SRST) tool for PrEP 3) STI laboratory diagnostic testing: Regardless of HIV serostatus, vaginal swabs will be collected to test for chlamydia, gonorrhea, trichomonas, and human papilloma virus. Syphilis testing will be performed using blood samples participants provided in the Rakai Community Cohort Study. Participants who test positive for a curable sexually transmitted infection (chlamydia, gonorrhea, trichomonas, or syphilis) OR who screen eligible for PrEP using the Ministry of Health SRST AND are HIV- will be referred for same-day PrEP initiation. Participants who have symptoms indicative of STIs or who test positive for an STI will be provided with free treatment, as will the partner(s).

IN-STEP Intervention

Self-reported risk screening for PrEP and syndromic management for STIs OTHER

This active comparator (control) arm will receive the following: 1) Standard-of-care STI symptom screening: Regardless of HIV serostatus, participants will be asked if any STI symptoms 2) Syphilis testing for pregnant participants: Regardless of HIV serostatus, syphilis testing will be performed using blood samples provided in the Rakai Community Cohort Study. 3) PrEP screening (if HIV- only): Participants will be screened for PrEP eligibility using the standard-care Ministry Health self-reported risk screening (SRST) tool for PrEP. Participants who screen eligible for PrEP using the Ministry of Health SRST OR pregnant participant's who test positive for syphilis AND are HIV- will be referred for same-day PrEP initiation. Participants who have symptoms indicative of STIs or who test positive for syphilis will be provided with free treatment, as will the partner(s).

Standard-of-Care

Eligibility Criteria

• Age: 15 Years - 39 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Sexually active females aged 15-39 years,
• resident in Rakai Community Cohort Study (RCCS) communities and who have participated in the most recent RCCS survey will be eligible to participate irrespective of their HIV serostatus.
• Pregnant women will be included in this study
• Additionally, eligibility criteria include participation in the most recent RCCS with consent to store and test plasma specimens collected during the RCCS visit,
• consent to be re-contacted for future studies, and
• willingness to be randomized in IN-STEP.

You may not qualify if:

• Individuals incapable of providing consent or
• not meeting the above criteria will be excluded from the study.

Sponsors & Collaborators

• Johns Hopkins University: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• Abbott: collaborator
• Bill and Melinda Gates Foundation: collaborator

Study Sites (1)

Rakai Health Sciences Program

Kalisizo, Uganda

RECRUITING

MeSH Terms

Conditions

Sexually Transmitted Diseases

Condition Hierarchy (Ancestors)

Communicable Diseases; Infections; Genital Diseases; Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Mary Kathryn Grabowski, Associate Professor, PhD

  Johns Hopkins School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mary Kathryn Grabowski, Associate Professor, PhD

CONTACT

443-287-5736; mgrabow2@jh.edu

Ronald M Galiwango, Ugandan PI, PhD

CONTACT

rmgaliwango@rhsp.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2024
• First Posted: December 19, 2024
• Study Start: September 8, 2025
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): January 31, 2029
• Last Updated: September 15, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: After publication of study outcomes
• Access Criteria: E-mail PI

Locations

UG (1)